Analysis of shared common genetic risk between amyotrophic lateral sclerosis and epilepsy

Because hyper-excitability has been shown to be a shared pathophysiological mechanism, we used the latest and largest genome-wide studies in amyotrophic lateral sclerosis (n = 36,052) and epilepsy (n = 38,349) to determine genetic overlap between these conditions. First, we showed no significant genetic correlation, also when binned on minor allele frequency. Second, we confirmed the absence of polygenic overlap using genomic risk score analysis. Finally, we did not identify pleiotropic variants in meta-analyses of the 2 diseases. Our findings indicate that amyotrophic lateral sclerosis and epilepsy do not share common genetic risk, showing that hyper-excitability in both disorders has distinct origins

Comparazioni e riflessioni tra il sistema italiano e quello sudafricano a seguito dell'esperienza di implementazione del budget maturata presso il Joannesburg Hospital

The introduction of one of the control process management tools in the biggest South African Universitary hospital, after over 15 years from the introduction of the management in the Italian public health organization, have allowed the team to perform a critical revision of the budget tool condition in Italy. The context analysis in the African country shows remarkable differences in comparison with our country. First of all, the ten percent less of personnel costs on the total hospital costs, requiring a different management tool from the one of the Italian model. The parallelism of the implementing process, instead, shows repeated lacks overlapping with the European ones. Commitments not clear and not keep as promise, lack of programming in the implementing process, lack of organic management approach as request of the clinical governance are the main results of the study.L’introduzione di uno degli strumenti manageriali per il ciclo di programmazione e controllo nel più grande ospedale universitario sudafricano, a distanza di oltre 15 anni dall’introduzione del processo di aziendalizzazione in sanità, ha permesso di rivedere criticamente lo stato dell’arte dell’applicazione in Italia. L’analisi del contesto nel Paese africano evidenzia notevoli differenze rispetto al nostro Paese, prima tra tutte i meno 10 punti percentuali di costo del personale sui costi totali, richiedendo la costruzione di uno strumento diverso dai modelli italiani. Il parallelismo del contorno applicativo, invece, mostra mancanze ripetute e sovrapponibili con quelle osservate in Europa. Mandati non chiari e non mantenuti, assenza di una precisa programmazione all’introduzione dello strumento, mancanza di disegno organico nella gestione, come invece richiesto dalla Clinical Governance, sono stati tra i principali risultati dell’osservazione

Un nuovo modello organizzativo ospedaliero pubblico: il week hospital sovradipartimentale

Proceeding with the description of innovative hospital organizational experiences, the article analyse preliminary data of the week hospital implementation model in the CTO - M. Adelaide hospital of Turin. The organizational change, driven by internal problems and by external benchmarking with others innovative models in orthopaedic hospitals, if planned and managed properly through coherent operational tools, proves its usefulness, even within the complex context of the operating theatre.Continuando a percorrere il filone delle esperienze organizzative innovative, in ambito sanitario, si presentano, in questo articolo, i primi dati derivanti dell'implementazione del modello organizzativo di week hospital, all'interno dell'A.O. CTO - M. Adelaide di Torino. Il cambiamento organizzativo, dettato da problematiche interne e da opportunità di confronti esterni con modelli innovativi sperimentati da altre strutture, se pianificato e gestito con leve operative coerenti e corrette, si dimostra utile e proficuo, anche nel complesso contesto delle attività di sala operatoria

Correlation of BRAF mutational status with clinical characteristics and survival outcomes of patients with ameloblastoma: the experience of 11 Italian centres

Background: Ameloblastoma is a rare odontogenic tumor with an aggressive local behavior. Mutations in the mitogen-activated protein kinase (MAPK) pathway, namely BRAF V600E mutations, are a common finding. To date there is no clear correlation between BRAF V600 mutation and clinical outcome. Methods: We retrospectively reviewed records of all patients undergoing surgery for ameloblastoma between February 2017 and March 2019 at 11 participating Italian centers. The primary endpoints of the study were to determine the BRAF mutational status in primitive and relapsed ameloblastoma, and to assess the relapse free interval (RFI); the secondary endpoint was to investigate the correlation of BRAF mutational status with clinical characteristics and survival outcomes. Results: Overall, 74 patients were included: 33 (44.5%) were BRAF wild type and 41 (55.4%) BRAFV600 mutated. BRAFV600 mutated ameloblastomas were more frequently in younger patients (p=0.0031), located at mandible site (p=0.0009), and with unicystic histotype. After a median follow up of 60 months, 21 (28.3%) patients relapsed (30.3% and 26.8% of in the BRAF wild type and BRAF mutated cases, respectively). At univariable Cox models, none of the analyzed variables, including microscopic margin involvement, appeared to be correlated with RFI. Conclusions: Local recurrence occurs in 30% of patients with ameloblastoma. BRAFV600 mutation is associated with younger age, a mandible site of the disease and with unicystic histotype. Neither BRAF mutation nor microscopic involved margins are associated with RFI. Further studies are needed to elucidate outcomes of this rare disease according to clinical, histopathological and comprehensive molecular features

Early weight loss in amyotrophic lateral sclerosis: outcome relevance and clinical correlates in a population-based cohort

Objectives: To assess the role of body mass index (BMI) and of the rate of weight loss as prognostic factors in amyotrophic lateral sclerosis (ALS) and to explore the clinical correlates of weight loss in the early phases of the disease. Methods: The study cohort included all ALS patients in Piemonte/Valle d'Aosta in the 2007-2011 period. Overall survival and the probability of death/tracheostomy at 18 months (logistic regression model) were calculated. Results: Of the 712 patients, 620 (87.1%) were included in the study. Patients ' survival was related to the mean monthly percentage of weight loss at diagnosis (p<0.0001), but not to pre-morbid BMI or BMI at diagnosis. Spinal onset patients with dysphagia at diagnosis had a median survival similar to bulbar onset patients. About 20% of spinal onset patients without dysphagia at diagnosis had severe weight loss and initial respiratory impairment, and had a median survival time similar to bulbar onset patients. Conclusions: The rate of weight loss from onset to diagnosis was found to be a strong and independent prognostic factor in ALS. Weight loss was mainly due to the reduction of nutritional intake related to dysphagia, but a subgroup of spinal onset patients without dysphagia at diagnosis had a severe weight loss and an outcome similar to bulbar patients. According to our findings, we recommend that in clinical trials patients should be stratified according to the presence of dysphagia at the time of enrolment and not by site of onset of symptoms

Analysis of shared common genetic risk between amyotrophic lateral sclerosis and epilepsy

Because hyper-excitability has been shown to be a shared pathophysiological mechanism, we used the latest and largest genome-wide studies in amyotrophic lateral sclerosis (n = 36,052) and epilepsy (n = 38,349) to determine genetic overlap between these conditions. First, we showed no significant genetic correlation, also when binned on minor allele frequency. Second, we confirmed the absence of polygenic overlap using genomic risk score analysis. Finally, we did not identify pleiotropic variants in meta-analyses of the 2 diseases. Our findings indicate that amyotrophic lateral sclerosis and epilepsy do not share common genetic risk, showing that hyper-excitability in both disorders has distinct origins